Targeting tumor-resident mast cells for effective anti-melanoma immune responses

Kaesler, Susanne and Wölbing, Florian and Kempf, Wolfgang Eberhard and Skabytska, Yuliya and Köberle, Martin and Volz, Thomas and Sinnberg, Tobias and Amaral, Teresa and Möckel, Sigrid and Yazdi, Amir and Metzler, Gisela and Schaller, Martin and Hartmann, Karin and Weide, Benjamin and Garbe, Claus and Rammensee, Hans-Georg and Röcken, Martin and Biedermann, Tilo. (2019) Targeting tumor-resident mast cells for effective anti-melanoma immune responses. JCI insight, 4 (19). e125057.

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Official URL: https://edoc.unibas.ch/72202/

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Immune checkpoint blockade has revolutionized cancer treatment. Patients developing immune mediated adverse events, such as colitis, appear to particularly benefit from immune checkpoint inhibition. Yet, the contributing mechanisms are largely unknown. We identified a systemic LPS signature in melanoma patients with colitis following anti-cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4) checkpoint inhibitor treatment and hypothesized that intestinal microbiota-derived LPS contributes to therapeutic efficacy. Because activation of immune cells within the tumor microenvironment is considered most promising to effectively control cancer, we analyzed human and murine melanoma for known sentinels of LPS. We identified mast cells (MCs) accumulating in and around melanomas and showed that effective melanoma immune control was dependent on LPS-activated MCs recruiting tumor-infiltrating effector T cells by secretion of CXCL10. Importantly, CXCL10 was also upregulated in human melanomas with immune regression and in patients with colitis induced by anti-CTLA-4 antibody. Furthermore, we demonstrate that CXCL10 upregulation and an MC signature at the site of melanomas are biomarkers for better patient survival. These findings provide conclusive evidence for a "Trojan horse treatment strategy" in which the plasticity of cancer-resident immune cells, such as MCs, is used as a target to boost tumor immune defense.
Faculties and Departments:03 Faculty of Medicine > Bereich Spezialfächer (Klinik) > Dermatologie USB > Allergologie (Hartmann)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Spezialfächer (Klinik) > Dermatologie USB > Allergologie (Hartmann)
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Allergy and Immunity (Hartmann)
UniBasel Contributors:Hartmann, Karin
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Society for Clinical Investigation
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:09 Nov 2020 16:24
Deposited On:09 Nov 2020 16:24

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